title: Cytotoxicity and DNA cleavage with core-shell nanocomposites functionalized by a KH domain DNA binding peptide.
abstract: A nanoconjugate was composed of metal oxide nanoparticles decorated with peptides and fluorescent dye and tested for DNA cleavage following UV light activation. The peptide design was based on a DNA binding domain, the so called KH domain of the hnRNPK protein. This "KH peptide" enabled cellular uptake of nanoconjugates and their entry into cell nuclei. The control nanoconjugate carried no peptide; it consisted only of the metal oxide nanoparticle prepared as Fe3O4@TiO2 nanocomposite and the fluorescent dye alizarin red S. These components of either construct are responsible for nanoconjugate activation by UV light and the resultant production of reactive oxygen species (ROS). Production of ROS at different subcellular locations causes damage to different components of cells: only nanoconjugates inside cell nuclei can be expected to cause DNA cleavage. Degradation of cellular DNA with KH peptide decorated nanoconjugates exceeded the DNA damage obtained from control, no-peptide nanoconjugate counterparts. Moreover, caspase activation and cell death were more extensive in the same cells.
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, University of Alexandria Medical School, Azarita Medical Campus, Champollion Street, Khartoum Square, Alexandria, Egypt. dr_remon77@yahoo.com.
authors.forename: Remon
authors.initials: R
authors.lastname: Bazak
authors.forename: Jan
authors.initials: J
authors.lastname: Ressl
authors.forename: Sumita
authors.initials: S
authors.lastname: Raha
authors.forename: Caroline
authors.initials: C
authors.lastname: Doty
authors.forename: William
authors.initials: W
authors.lastname: Liu
authors.forename: Beau
authors.initials: B
authors.lastname: Wanzer
authors.forename: Seddik Abdel
authors.initials: SA
authors.lastname: Salam
authors.forename: Samy
authors.initials: S
authors.lastname: Elwany
authors.forename: Tatjana
authors.initials: T
authors.lastname: Paunesku
authors.forename: Gayle E
authors.initials: GE
authors.lastname: Woloschak
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects / Q000528:radiation effects; D052203:Ferrosoferric Oxide / Q000737:chemistry; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity; D018613:Microscopy, Confocal; D053761:Nanocomposites / Q000737:chemistry* / Q000633:toxicity; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species / Q000378:metabolism; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism; D014025:Titanium / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D010455:Peptides; D017382:Reactive Oxygen Species; D012261:Ribonucleoproteins; C072074:HNRNPK protein, human; C009495:titanium dioxide; D004247:DNA; D014025:Titanium; D052203:Ferrosoferric Oxide